Document Detail


Diagnosis by serendipity: Cushing syndrome attributable to cortisol-producing adrenal adenoma as the initial manifestation of multiple endocrine neoplasia type 1 due to a rare splicing site MEN1 gene mutation.
MedLine Citation:
PMID:  18753104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To report a case that highlights the potential for Cushing syndrome to be the first manifestation of multiple endocrine neoplasia type 1 (MEN 1) syndrome and to describe the rare underlying genetic mutation and the heterogeneous manifestations of the syndrome within the same family. METHODS: We present a case report including biochemical and radiologic findings, review family data, and discuss the results of genetic analyses. RESULTS: A 16-year-old girl who was not known to have any medical illness and had no known family history of MEN 1 syndrome presented with Cushing syndrome attributable to a cortisol-producing adrenal adenoma. During her evaluation, she was found to have primary hyperparathyroidism and a pituitary microprolactinoma. These findings raised the possibility of MEN 1 syndrome. She did not have clinical, biochemical, or radiologic evidence of islet cell pancreatic tumors. Family screening showed that her father had evidence of primary hyperparathyroidism, mild hyperprolactinemia, normal findings on magnetic resonance imaging of the pituitary, and a 1.2-cm nodule in the tail of the pancreas in conjunction with slight elevation of serum insulin and normal gastrin levels. The patient's 5 siblings had evidence of primary hyperparathyroidism, and 2 of them also had mild hyperprolactinemia. Genetic screening confirmed the presence of a MEN1 gene missense G to A mutation in the patient, her father, and her siblings at the splicing site of intron 6 (IVS6+1G>A). This mutation leads to frameshift and truncation of the MEN1 gene. CONCLUSION: In MEN 1, Cushing syndrome is an extremely rare and usually late manifestation. Most cases are due to corticotropin-producing pituitary adenomas. Although Cushing syndrome generally develops years after the more typical manifestations of MEN 1 appear, it may be the primary manifestation of MEN 1 syndrome. There is considerable heterogeneity in the manifestations of MEN 1, even within a family having the same genetic mutation.
Authors:
Ali S Alzahrani; Nojoud Al-Khaldi; Yufei Shi; Roua A Al-Rijjal; Minjing Zou; Essa Y Baitei; Tarek Amin
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists     Volume:  14     ISSN:  1934-2403     ISO Abbreviation:  Endocr Pract     Publication Date:    2008 Jul-Aug
Date Detail:
Created Date:  2008-08-28     Completed Date:  2009-01-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607439     Medline TA:  Endocr Pract     Country:  United States    
Other Details:
Languages:  eng     Pagination:  595-602     Citation Subset:  IM    
Affiliation:
Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adrenocortical Adenoma / complications,  genetics,  pathology*
Cushing Syndrome / diagnosis*,  etiology,  genetics
Female
Humans
Hydrocortisone / secretion*
Multiple Endocrine Neoplasia Type 1 / complications,  genetics,  pathology*
Mutation
Proto-Oncogene Proteins / genetics
Chemical
Reg. No./Substance:
0/MEN1 protein, human; 0/Proto-Oncogene Proteins; 50-23-7/Hydrocortisone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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